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Cyclophosphamide (CP), a commonly used alkylating chemotherapeutic agent, is known for its pronounced oxidative stress-related toxicity, which limits its therapeutic application. As a natural substance rich in antioxidants, honey has attracted attention for its potential to counteract such toxic side effects. This study evaluated the protective effects of two floral varieties of Moroccan honey against CP-induced genotoxicity and tissue damage in mice. Male mice were pre-treated with honey before receiving a single dose of CP. The genotoxic and cytotoxic impacts were assessed through bone marrow micronucleus assays, specifically examining the frequency of micronucleated polychromatic erythrocytes (MNPCE) and the ratio of polychromatic to normochromatic erythrocytes (PCE/NCE). Biochemical markers, including serum levels of alanine aminotransferase, aspartate aminotransferase, urea, and creatinine, along with histopathological analysis of liver and kidney tissues, were used to measure systemic damage. The results demonstrated that CP significantly increased MNPCE levels and decreased the PCE/NCE ratio, confirming its genotoxic and cytotoxic properties. However, pre-treatment with either type of honey significantly mitigated these effects, restoring parameters toward normal levels. The honeys also helped normalize biochemical markers and reduced hepatic damage characterized by steatosis, apoptosis, necrosis, and inflammatory cell infiltration. Overall, this study highlights the potential of Moroccan honeys as natural protective agents capable of reducing CP-induced genotoxicity and organ damage, supporting their role as potential adjuvants in chemotherapy protocols.
